equipment and instrumentation necessary for organic synthesis and small molecule characterization including a Shimadzu LC-Mass spectrometer, a Varian 300-MHz 'H(13C, I5N, 31P)-nmr spectrometer and a Biacore plasmon resonance detector. The small molecules to be synthesized for each project will.be based on known parent compounds with previously demonstrated activity. The parent compounds include JTV-519 for the Marks project, rottlerin for the Marx project, R-L3 and acrylamide derivatives for the Kass project, and JTV [unreadable]derivatives and agents to cross-link and label proteins for the Karlin project. As required for each project, the Core will prepare specific classes of derivatives that will serve as tools to define structure and activity. The range of classes will include tethered analogs for affinity purification, radio-labeled analogs for binding studies, and analogs for photoaffmity labeling that contain a radiolabel or a tether for affinity purification. The Core will also produce selected parent compounds and analogs on a preparative scale for in vivo testing in the Animal Core Facility of the PPG. The ability to tailor molecules in response to biological and biochemical activity provides a potent tool for investigating the allosteric modulation of ion channels. JTV Rottlerin JTV R-L3 Class of Molecule to be prepared: (Marks) (Marx) (Karlin) (Kass) Parent Compound X X X Analogs for Structure-Activity II. Studies X X 3H- Labeled Analogs X IV. Tethered Analogs for Affinity Purification or Biacore Assay X V. Radiolabeled Photoaffinity Analogs X VI. Photoaffinity Analogs Tethered for Affinity Purification X PHS 398/2590 (Rev. 09/04) Page 2~ Continuation Format Page